The incidences of type 1 and type 2 diabetes are increasing rapidly within the United States and throughout the world, and there are no curative treatments. Researchers in this grant application, all members of the NIH-supported Diabetes Research Center (DRC) (King, George) at the Joslin Diabetes Center, study the cellular pathogenesis of type 1 and type 2 diabetes, with the long term goal of developing cell based diabetes therapies. An essential and powerful technique required for the diverse research described in this application is high throughput polychromatic flow cytometry. To address this need, this grant application requests funds to support the purchase of a BD LSRFortessa. The flow cytometer is a powerful tool to detect, analyze and characterize virtually any cell population based on numerous cell surface or intracellular parameters. Investigators at Joslin require a new flow cytometer with enhanced capability to detect new fluorochromes, to facilitate high throughput analyses, and to increase the reliability of the flow core in serving its users. The proposed FACS instrument will be used by at least 15 different labs at Joslin and Harvard affiliate institutions, and will support research projects focused on hematopoietic stem and progenitor populations, skeletal muscle progenitor populations, insulin-producing beta cells, white adipocyte and brown adipocyte populations and their progenitors, macrophages, mature and immature T cell lineages, and thymic epithelial cells and their progenitors. This analyzer will be housed in the Joslin Diabetes Center Flow Cytometry Core facility, and will be maintained by two full-time flow cytometrists. The cross-fertilization of ideas that occurs in a widely utilized, state-of-the-art flow cytometry core is one of the significant benefits of having modern flow cytometry core shared by a community of interactive labs.